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Frontiers in Immunology 2023Activation of pancreatic stellate cells (PSCs) to cancer-associated fibroblasts (CAFs) is responsible for the extensive desmoplastic reaction observed in PDAC stroma: a...
Activation of pancreatic stellate cells (PSCs) to cancer-associated fibroblasts (CAFs) is responsible for the extensive desmoplastic reaction observed in PDAC stroma: a key driver of pancreatic ductal adenocarcinoma (PDAC) chemoresistance leading to poor prognosis. Specialized pro-resolving mediators (SPMs) are prime modulators of inflammation and its resolution, traditionally thought to be produced by immune cells. Using liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based lipid mediator profiling PSCs as well as primary human CAFs express enzymes and receptors to produce and respond to SPMs. Human PSC/CAF SPM secretion profile can be modulated by rendering these cells activated [transforming growth factor beta (TGF-β)] or quiescent [all- retinoic acid (ATRA)]. ATRA-induced nuclear translocation of arachidonate-15-lipoxygenase (ALOX15) was linked to increased production of n-3 docosapentaenoic acid-derived Resolvin D5 (RvD5), among other SPMs. Inhibition of RvD5 formation increases cancer cell invasion, whereas addback of this molecule reduced activated PSC-mediated cancer cell invasion. We also observed that circulating concentrations of RvD5 levels were decreased in peripheral blood of metastatic PDAC patients when compared with those measured in plasma of non-metastatic PDAC patients. Together, these findings indicate that RvD5 may regulate cancer-stroma cross-talk and invasion.
Topics: Humans; Arachidonate 15-Lipoxygenase; Pancreatic Stellate Cells; Chromatography, Liquid; Tandem Mass Spectrometry; Pancreatic Neoplasms; Carcinoma, Pancreatic Ductal; Tretinoin; Neoplasm Invasiveness
PubMed: 38035115
DOI: 10.3389/fimmu.2023.1248547 -
Journal of Obstetrics and Gynaecology :... Dec 2023This study was designed to investigate the association between nutrients and female infertility.
BACKGROUND
This study was designed to investigate the association between nutrients and female infertility.
METHODS
A cross-sectional study on 18-45 years of age reproductive-age women was conducted using the data from the National Health and Nutrition Examination Surveys (NHANES) for the periods 2013-2014 and 2015-2016. Multivariate logistic regression analysis was performed to evaluate the association between nutrients and female infertility. Subgroup analysis was applied to the body mass index (BMI). Results were summarised using an odds ratio (OR) with a 95% confidence interval (CI).
RESULTS
Of the total 1713 women, 204 women (11.91%) were infertile. The result demonstrated that higher intake of carbohydrate (OR: 0.46, 95% CI: 0.24-0.86, = 0.018), vitamin A (OR: 0.44, 95% CI: 0.24-0.80, = 0.009), vitamin C (OR: 0.48, 95% CI: 0.26-0.88, = 0.020), magnesium (OR: 0.36, 95% CI: 0.17-0.76, = 0.009), iron (OR: 0.43, 95% CI: 0.23-0.82, = 0.012), lycopene (OR: 0.55, 95% CI: 0.33-0.91, = 0.022), and total folate (OR: 0.38, 95% CI: 0.20-0.70, = 0.003) were associated with a lower risk of female infertility. The subgroup analysis also reported that intakes of vitamin A, vitamin C, and lycopene were related to a lower risk of female infertility among women with a BMI being 18.5-24.9 kg/m. Among women with BMI > 24.9 kg/m, high intakes of magnesium, iron and total folate were associated with a decreased risk of female infertility.
CONCLUSIONS
The intake of several nutrients is associated with a decreased risk of female infertility. These findings provide insight into potentially modifiable lifestyle factors associated with female infertility.
Topics: Female; Humans; Diet; Nutrition Surveys; Magnesium; Vitamin A; Infertility, Female; Cross-Sectional Studies; Lycopene; Eating; Vitamins; Folic Acid; Ascorbic Acid; Iron
PubMed: 38010776
DOI: 10.1080/01443615.2023.2285025 -
Clinical, Cosmetic and Investigational... 2023Isotretinoin (ISO) is a powerful vitamin A derivative that offers the potential for treatment of permanent remission of acne; however, its potential side effects on both... (Review)
Review
Isotretinoin (ISO) is a powerful vitamin A derivative that offers the potential for treatment of permanent remission of acne; however, its potential side effects on both physiological and psychological aspects limit its application. This article reviews the side effects of ISO from physiological and psychological aspects in detail, to better screen the suitable population of ISO and improve the efficiency of clinical treatment. Our findings indicate that ISO may cause teratogenicity, skin reactions, ocular reactions, changes in blood indicators, and occasional acne fulminans. To optimize clinical treatment, more attention should be paid to identifying the specific conditions under which these reactions occur, how severe they are, and how they subside to alleviate patient concerns. Regarding the controversial issue of psychological side effects caused by ISO, researchers should shift their focus to the psychological problems that acne itself may cause.
PubMed: 37483471
DOI: 10.2147/CCID.S416267 -
Nutrients Dec 2023This systematic review aims to assess whether edible vegetable oils and fats fortified with vitamin A and/or D are effective and safe in improving vitamin intake and... (Meta-Analysis)
Meta-Analysis Review
Benefits and Harms of Edible Vegetable Oils and Fats Fortified with Vitamins A and D as a Public Health Intervention in the General Population: A Systematic Review of Interventions.
This systematic review aims to assess whether edible vegetable oils and fats fortified with vitamin A and/or D are effective and safe in improving vitamin intake and ameliorating deficiency states in the general population. In November 2022, we systematically searched MEDLINE, Cochrane CENTRAL, Scopus, Global Index Medicus, ClinicalTrials.gov, and WHO ICTRP (International Clinical Trials Registry Platform) for randomized controlled trials (RCT) and non-randomized studies of interventions (NRSI) investigating the fortification of edible vegetable oils and fats with either vitamin A or vitamin D or both as compared to the same vegetable oils and/or fats without vitamin A and D fortification or no interventions, in the general population, without age restriction. We assessed the methodological quality of included RCTs using Cochrane's risk of bias tool 2.0 and of NRSIs using ROBINS-I tool. We performed random-effects meta-analysis and assessed certainty of evidence using GRADE. We included eight studies. Available evidence showed no significant effect of fortification with vitamin A on serum retinol levels (RCTs: MD 0.35 µmol/L, 95% CI -0.43 to 1.12; two trials; 514 participants; low-certainty evidence; CCTs: MD 0.31 µmol/L, 95% CI -0.18 to 0.80; two trials; 205 participants; very low-certainty evidence) and on subclinical vitamin A deficiency. Low-certainty evidence showed no effect of vitamin D fortification on serum 25-hydroxy vitamin D concentration (MD 6.59 nmol/L, 95% CI -6.89 to 20.07; one trial; 62 participants). In conclusion, vitamin A-fortified vegetable oils and fats may result in little to no difference in serum retinol levels in general populations. The dose of vitamin A used in the trials may be safe but may not be sufficient to reduce subclinical vitamin A deficiency. Further, the evidence suggests that vitamin D fortification results in little to no difference in serum 25-hydroxy vitamin D concentration. Several aspects of providing fortified oils and fats to the general population as a public health intervention should be further investigated, including optimal fortification dose, effects on vitamin D deficiency and its clinical symptoms and potential adverse effects.
Topics: Humans; Vitamins; Vitamin A; Vitamin A Deficiency; Vegetables; Public Health; Plant Oils; Food, Fortified; Vitamin K; Vitamin D
PubMed: 38140394
DOI: 10.3390/nu15245135 -
Journal of Experimental & Clinical... Aug 2023Acute myeloid leukemia (AML) patients bearing the ITD mutation in the tyrosine kinase receptor FLT3 (FLT3-ITD) present a poor prognosis and a high risk of relapse....
BACKGROUND
Acute myeloid leukemia (AML) patients bearing the ITD mutation in the tyrosine kinase receptor FLT3 (FLT3-ITD) present a poor prognosis and a high risk of relapse. FLT3-ITD is retained in the endoplasmic reticulum (ER) and generates intrinsic proteotoxic stress. We devised a strategy based on proteotoxic stress, generated by the combination of low doses of the differentiating agent retinoic acid (R), the proteasome inhibitor bortezomib (B), and the oxidative stress inducer arsenic trioxide (A).
METHODS
We treated FLT3-ITD AML cells with low doses of the aforementioned drugs, used alone or in combinations and we investigated the induction of ER and oxidative stress. We then performed the same experiments in an in vitro co-culture system of FLT3-ITD AML cells and bone marrow stromal cells (BMSCs) to assess the protective role of the niche on AML blasts. Eventually, we tested the combination of drugs in an orthotopic murine model of human AML.
RESULTS
The combination RBA exerts strong cytotoxic activity on FLT3-ITD AML cell lines and primary blasts isolated from patients, due to ER homeostasis imbalance and generation of oxidative stress. AML cells become completely resistant to the combination RBA when treated in co-culture with BMSCs. Nonetheless, we could overcome such protective effects by using high doses of ascorbic acid (Vitamin C) as an adjuvant. Importantly, the combination RBA plus ascorbic acid significantly prolongs the life span of a murine model of human FLT3-ITD AML without toxic effects. Furthermore, we show for the first time that the cross-talk between AML and BMSCs upon treatment involves disruption of the actin cytoskeleton and the actin cap, increased thickness of the nuclei, and relocalization of the transcriptional co-regulator YAP in the cytosol of the BMSCs.
CONCLUSIONS
Our findings strengthen our previous work indicating induction of proteotoxic stress as a possible strategy in FLT3-ITD AML therapy and open to the possibility of identifying new therapeutic targets in the crosstalk between AML and BMSCs, involving mechanotransduction and YAP signaling.
Topics: Humans; Animals; Mice; Tretinoin; Cytoprotection; Disease Models, Animal; Mechanotransduction, Cellular; Proteotoxic Stress; Ascorbic Acid; Cell Death
PubMed: 37653435
DOI: 10.1186/s13046-023-02793-z -
International Journal of Chronic... 2023Vitamins and carotenoids are essential in preventing and treating chronic obstructive pulmonary disease (COPD). This study investigated the associations between serum...
PURPOSE
Vitamins and carotenoids are essential in preventing and treating chronic obstructive pulmonary disease (COPD). This study investigated the associations between serum vitamins, carotenoids, and COPD in adults aged ≥ 40 years in the United States.
METHODS
We selected 3487 participants aged ≥40 from the NHANES (2017-2018) and used demographic analysis, sensitivity tests, and different weighted multivariate regression models to investigate the relationship between serum vitamins, carotenoids, and COPD.
RESULTS
Subjects in the highest tertile of serum vitamin C, vitamin E (α-tocopherol), α-carotene, trans-β-carotene, and cis-β-carotene had a 50%, 35%, 51%, 54%, and 51% lower risk of COPD than those in the lowest tertile (P for trend: P=0.0005, <0.0001, 0.0054, 0.0066, and 0.0049). Unfortunately, no significant correlation was found for serum vitamin D levels.
CONCLUSION
Our analysis of nationally representative data from 3487 participants showed that serum levels of vitamin C, vitamin E (α-tocopherol), α-carotene, and β-carotene were negatively associated with the incidence of COPD in adults over 40 years of age in the US The findings highlighted the importance of antioxidant vitamins and carotenoids in respiratory health, while the data showed no significant correlation between vitamin D (25-OHD) and the incidence of COPD.
Topics: Adult; Humans; United States; Middle Aged; beta Carotene; alpha-Tocopherol; Pulmonary Disease, Chronic Obstructive; Nutrition Surveys; Carotenoids; Antioxidants; Vitamins; Vitamin E; Vitamin A; Ascorbic Acid; Vitamin D
PubMed: 38107596
DOI: 10.2147/COPD.S432995 -
Journal of Proteome Research Jul 2023-Palmitoylation is the covalent attachment of C14:0-C22:0 fatty acids (mainly C16:0 palmitate) to cysteines via thioester bonds. This lipid modification is highly...
-Palmitoylation is the covalent attachment of C14:0-C22:0 fatty acids (mainly C16:0 palmitate) to cysteines via thioester bonds. This lipid modification is highly abundant in neurons, where it plays a role in neuronal development and is implicated in neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and Huntington's disease. The knowledge of -palmitoylation in neurodevelopment is limited due to technological challenges in analyzing this highly hydrophobic protein modification. Here, we used two orthogonal methods, acyl-biotin exchange (ABE) and lipid metabolic labeling (LML), to identify -palmitoylated proteins and sites during retinoic acid-induced neuronal differentiation of SH-SY5Y cells. We identified 2002 putative -palmitoylated proteins in total, of which 650 were found with both methods. Significant changes in the abundance of -palmitoylated proteins were detected, in particular for several processes and protein classes that are known to be important for neuronal differentiation, which include proto-oncogene tyrosine-protein kinase receptor (RET) signal transduction, SNARE protein-mediated exocytosis, and neural cell adhesion molecules. Overall, -palmitoylation profiling by employing ABE and LML in parallel during RA-induced differentiation of SH-SY5Y cells revealed a subset of high confidence bona fide -palmitoylated proteins and suggested an important role for -palmitoylation in neuronal differentiation.
Topics: Humans; Tretinoin; Lipoylation; Neuroblastoma; Cell Differentiation; Proteins; Lipids; Cell Line, Tumor
PubMed: 37294931
DOI: 10.1021/acs.jproteome.3c00151 -
Food & Nutrition Research 2023Vitamin A refers to a group of fat-soluble compounds with retinol activity, including all- retinol and pro-vitamin A carotenoids. Bioactive compounds include retinal and... (Review)
Review
Vitamin A refers to a group of fat-soluble compounds with retinol activity, including all- retinol and pro-vitamin A carotenoids. Bioactive compounds include retinal and all- retinoic acid with important functions in vision, immune function, growth, and development. The literature search that was performed for the current scoping review yielded a total of seven publications relevant to setting the recommended daily intake for vitamin A. In total, six publications assessed the relationship of serum retinol and/or dietary vitamin A intake with fracture risk ( = 2), cancer ( = 3), and deficiency after bariatric surgery ( = 1). One additional report by the European Food Safety Administration (EFSA) with updated average requirements was included. The outcomes-based systematic reviews and meta-analyses showed positive associations for vitamin A intake and serum retinol with risk of hip fracture. Weak or inconclusive associations were observed for cancer or obesity. One publication by EFSA with updated estimated average requirements and population reference intakes for dietary vitamin A intakes was published in 2015. The EFSA recommendations and estimated average requirements are based on a European reference population, with body weights derived from an assumed body mass index of 22, which might be too low and not representative of the Nordic and Baltic populations, and consequently resulting in lower estimated average requirements and recommendations. In conclusion, there were limited new outcomes-based data for vitamin A and health outcomes.
PubMed: 38686175
DOI: 10.29219/fnr.v67.10229 -
Scientific Reports Sep 2023The aim of this randomized clinical trial was to evaluate the impact of all-trans retinoic acid (ATRA) in combination with non-intensive chemotherapy in older unfit... (Randomized Controlled Trial)
Randomized Controlled Trial
The aim of this randomized clinical trial was to evaluate the impact of all-trans retinoic acid (ATRA) in combination with non-intensive chemotherapy in older unfit patients (> 60 years) with newly diagnosed NPM1-mutated acute myeloid leukemia. Patients were randomized (1:1) to low-dose chemotherapy with or without open-label ATRA 45 mg/m, days 8-28; the dose of ATRA was reduced to 45 mg/m, days 8-10 and 15 mg/m, days 11-28 after 75 patients due to toxicity. Up to 6 cycles of cytarabine 20 mg/day s.c., bid, days 1-7 and etoposide 100 mg/day, p.o. or i.v., days 1-3 with (ATRA) or without ATRA (CONTROL) were intended. The primary endpoint was overall survival (OS). Between May 2011 and September 2016, 144 patients (median age, 77 years; range, 64-92 years) were randomized (72, CONTROL; 72, ATRA). Baseline characteristics were balanced between the two study arms. The median number of treatment cycles was 2 in ATRA and 2.5 in CONTROL. OS was significantly shorter in the ATRA compared to the CONTROL arm (p = 0.023; median OS: 5 months versus 9.2 months, 2-years OS rate: 7% versus 10%, respectively). Rates of CR/CRi were not different between treatment arms; infections were more common in ATRA beyond treatment cycle one. The addition of ATRA to low-dose cytarabine plus etoposide in an older, unfit patient population was not beneficial, but rather led to an inferior outcome.The clinical trial is registered at clinicaltrialsregister.eu (EudraCT Number: 2010-023409-37, first posted 14/12/2010).
Topics: Humans; Aged; Etoposide; Leukemia, Myeloid, Acute; Cytarabine; Tretinoin; Nuclear Proteins
PubMed: 37684299
DOI: 10.1038/s41598-023-41964-y -
Nutrients Dec 2023The present review deals with two main ingredients of energy/power drinks: B vitamins and glucuronolactone and their possible effect on the immune system. There is a... (Review)
Review
The present review deals with two main ingredients of energy/power drinks: B vitamins and glucuronolactone and their possible effect on the immune system. There is a strong relationship between the recommended daily dose of selected B vitamins and a functional immune system. Regarding specific B vitamins: (1) Riboflavin is necessary for the optimization of reactive oxygen species (ROS) in the fight against bacterial infections caused by and . (2) Niacin administered within normal doses to obese rats can change the phenotype of skeletal fibers, and thereby affect muscle metabolism. This metabolic phenotype induced by niacin treatment is also confirmed by stimulation of the expression of genes involved in the metabolism of free fatty acids (FFAs) and oxidative phosphorylation at this level. (3) Vitamin B5 effects depend primarily on the dose, thus large doses can cause diarrhea or functional disorders of the digestive tract whereas normal levels are effective in wound healing, liver detoxification, and joint health support. (4) High vitamin B6 concentrations (>2000 mg per day) have been shown to exert a significant negative impact on the dorsal root ganglia. Whereas, at doses of approximately 70 ng/mL, sensory symptoms were reported in 80% of cases. (5) Chronic increases in vitamin B12 have been associated with the increased incidence of solid cancers. Additionally, glucuronolactone, whose effects are not well known, represents a controversial compound. (6) Supplementing with D-glucarates, such as glucuronolactone, may help the body's natural defense system function better to inhibit different tumor promoters and carcinogens and their consequences. Cumulatively, the present review aims to evaluate the relationship between the selected B vitamins group, glucuronolactone, and the immune system and their associations to bioavailability, doses, and efficiency.
Topics: Animals; Rats; Vitamin B Complex; Niacin; Biological Availability; Glucuronates; Vitamin A; Vitamin K; Carcinogens
PubMed: 38201854
DOI: 10.3390/nu16010024